Biophysics of Disordered Protein/RNA Condensates

Biomolecular condensates are ubiquitous cellular assemblies comprised of proteins, RNA and other molecules, representing compartmentalization without the need for membranes. Rapidly expanding research over the past decade has uncovered roles of the physical properties of condensates in numerous cellular functions as well as misfunction. Here, I will discuss two strands of our work to uncover new mechanistic principles with broad relevance for the physics of biomolecular condensation formed from charged macromolecules. In one, our results reveal non-monotonic phase behavior (such as reentrant phase transitions) in RNA/protein/polyphosphate condensates, along with formation of dynamic substructures. Our results imply complex condensate control elements, with implications for potential feedback loops and other regulation in cellular processes. Second, we have made the exciting discovery that charged condensates can induce localized potentials in membranes, representing a novel electrical mechanism for regulation of membrane-related function in biology. In parallel, I will discuss our applications of cutting-edge single-molecule methods for these studies. Our results provide new insight into principles governing the complex physical behavior of condensates formed from charged biopolymers, with implications for cellular regulation and biotechnology.